Transcript GOLD - School of Medicine

Global Initiative for Chronic
Obstructive
L ung
Disease
GOLD Website Address
http://www.goldcopd.com
18/Oct/2005
Dr. David P. Breen
2
Facts About COPD

COPD is the 4th leading cause of death in the
United States (behind heart disease, cancer,
and cerebrovascular disease).

In 2000, the WHO estimated 2.74 million
deaths worldwide from COPD.

In 1990, COPD was ranked 12th as a burden
of disease; by 2020 it is projected to rank 5th.
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Leading Causes of Deaths
U.S. 1998
Cause of Death
Number
Heart Disease
724,269
Cancer
538,947
Cerebrovascular disease (stroke) 158,060
Respiratory Diseases (COPD)
114,381
Accidents
94,828
Pneumonia and influenza
93,207
Diabetes
64,574
Suicide
29,264
Nephritis
26,295
Chronic liver disease
24,936
18/Oct/2005All other causes of death Dr. David P. Breen
469,314
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
4
Percent Change in Age-Adjusted
Death Rates, U.S., 1965-1998
Proportion of 1965 Rate
3.0
3.0
2.5
2.5
Coronary
Heart
Disease
Stroke
Other CVD
COPD
All Other
Causes
–59%
–64%
–35%
+163%
–7%
1965 - 1998
1965 - 1998 5
2.0
2.0
1.5
1.5
1.0
1.0
0.5
0.5
0.0 0
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1965
- 1998
1965 - 1998
Dr.1965
David P.-Breen
1998
Age-Adjusted Death Rates for
COPD, U.S., 1960-1998
Deaths per 100,000
6060
White Male
5050
4040
Black Male
3030
White Female
2020
Black Female
1010
00
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1960
1960
1965
1965
1970
1970
P. Breen
1975 Dr. David
1980
1975
1980
1985
1985
1990
1990
1995
1995
6
2000
2000
Facts About COPD: U.S.

Between 1985 and 1995, the number of
physician visits for COPD increased from
9.3 to16 million.

The number of hospitalizations for COPD
in 2000 was estimated to be 726,000.

Medical expenditures in 2002 were
estimated to be $18.0 billion.
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Facts About COPD
 Cigarette smoking is the primary cause of
COPD.
 In the US 47.2 million people (28% of men and
23% of women) smoke.
 The WHO estimates 1.1 billion smokers
worldwide, increasing to 1.6 billion by 2025. In
low- and middle-income countries, rates are
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increasing at an alarming
rate.
Irish Figures




Diseases of the Respiratory system are the cause of
one in five deaths in Ireland today
In 1999 , Respiratory disease caused 7100 deaths:
3700 in men and 3400 in women
26% of respiratory deaths were due to COPD
=1846 COPD-related deaths
Clear social gradient: Respiratory mortality in the
lowest occupational class was 200% higher than
the highest occupational class
Inhale survey
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Clinically apparent disease
Subclinical/
undiagnosed disease
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COPD and Smoking
95% of COPD is caused by smoking
 45% of young Irish adults are current smokers
 Prevalence of current smokers is higher in
females (46.5% female v 44.2% male)
 30% of school-leavers smoke

ECRHS Group
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Smoking in Ireland
Adults
in 1973  29% in 1994  27% now
 highest in lowest SE groups
 declining more slowly in women than men
 43%
Children and teenagers
 1/10
6th class pupils smoke regularly, 15% boys, 5% girls
 1/2 6th class pupils have tried smoking
 smoking increases steadily in teens in both sexes
 30-35% of 17 yo Dublin schoolchildren smoke regularly,
equal in both sexes
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Lung Function decline
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Global Initiative for Chronic
Obstructive
L ung
Disease
GOLD Workshop Report:
Contents







Introduction
Definition and classification
Burden of COPD
Risk factors
Pathogenesis, pathology,
and pathophysiology
Management
Future research
Definition of COPD
Chronic obstructive pulmonary disease
(COPD) is a disease state characterized
by airflow limitation that is not fully
reversible. The airflow limitation is usually
both progressive and associated with an
abnormal inflammatory response of the
lungs to noxious particles or gases.
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Burden of COPD
Key Points

The burden of COPD is underestimated
because it is not usually recognized and
diagnosed until it is clinically apparent and
moderately advanced.

Prevalence, morbidity, and mortality vary
appreciably across countries but in all
countries where data are available, COPD
is a significant health problem in both men
and women.
Burden of COPD
Key Points
 The global burden of COPD will
increase enormously over the
foreseeable future as the toll from
tobacco use in developing countries
becomes apparent.
Burden of COPD
Key Points

The economic costs of COPD are high
and will continue to rise in direct relation
to the ever-aging population, the
increasing prevalence of the disease,
and the cost of new and existing medical
and public health interventions.
Direct and Indirect Costs of
COPD, 2002 (US $ Billions)

Direct Medical Cost:
$18.0

Total Indirect Cost:
– Mortality related IDC
– Morbidity related IDC
$ 14.1

Total Cost
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7.3
6.8
$32.1
Dr. David P. Breen
Source: NHLBI, NIH, DHHS
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Risk Factors for COPD
Host Factors
Genes (e.g. alpha1-antitrypsin
deficiency)
Hyperresponsiveness
Lung growth
Exposure
Tobacco smoke
Occupational dusts and chemicals
Infections
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Socioeconomic
status
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Pathogenesis of COPD
NOXIOUS AGENT
(tobacco smoke, pollutants, occupational agent)
Genetic factors
Respiratory
infection
Other
COPD
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Noxious particles
and gases
Host factors
Lung inflammation
Anti-oxidants
Oxidative stress
Anti-proteinases
Proteinases
Repair mechanisms
COPD pathology
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Causes of Airflow Limitation

Irreversible
Fibrosis and narrowing of the
airways
Loss of elastic recoil due to
alveolar destruction
Destruction of alveolar support
that maintains patency of small
airways
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Causes of Airflow Limitation

Reversible
 Accumulation of inflammatory cells,
mucus, and plasma exudate in bronchi
 Smooth muscle contraction in
peripheral and central airways
 Dynamic hyperinflation during exercise
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Objectives of COPD
Management
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
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Prevent disease progression
Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent and treat exacerbations
Prevent and treat complications
Reduce mortality
Minimize sideDr.effects
David P. Breen from treatment
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GOLD Workshop Report
Four Components of COPD
Management
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic
4. Manage exacerbations
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Assess and Monitor
Disease: Key Points

Diagnosis of COPD is based on a history of
exposure to risk factors and the presence
of airflow limitation that is not fully
reversible, with or without the presence of
symptoms.
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Assess and Monitor
Disease: Key Points

Patients who have chronic cough
and sputum production with a
history of exposure to risk factors
should be tested for airflow
limitation, even if they do not have
dyspnea.
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Assess and Monitor
Disease: Key Points
For the diagnosis and assessment of
COPD, spirometry is the gold standard.
 Health care workers involved in the
diagnosis and management of COPD
patients should have access to
spirometry.

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Assess and Monitor
Disease: Key Points

Measurement of arterial blood gas
tension should be considered in all
patients with FEV1 < 40% predicted
or clinical signs suggestive of
respiratory failure or right heart
failure.
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Diagnosis of COPD
EXPOSURE TO RISK
FACTORS
SYMPTOMS
cough
sputum
dyspnea
tobacco
occupation
indoor/outdoor pollution

SPIROMETRY
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Spirometry: Normal and COPD
0
FEV1
Normal
COPD
1
Liter
2
FVC
FEV1/ FVC
4.150
5.200
80 %
2.350
3.900
60 %
FEV1
3
COPD
4
FVC
FEV1
Normal
5
1
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2
3
FVC
4
Dr. David P. Breen
5
6
Seconds
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Factors Determining Severity
Of Chronic COPD
 Severity of symptoms
 Severity of airflow limitation
 Frequency and severity of exacerbations
 Presence of complications of COPD
 Presence of respiratory insufficiency
 Comorbidity
 General health status
 Number of medications needed to manage the
disease
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Classification by Severity
Stage
Characteristics
0: At risk
Normal spirometry
Chronic symptoms (cough, sputum)
I: Mild
FEV1/FVC < 70%; FEV1  80% predicted
With or without chronic symptoms (cough, sputum)
II: Moderate
FEV1/FVC < 70%; 50% FEV1 < 80% predicted
With or without chronic symptoms (cough, sputum, dyspnea)
III: Severe
FEV1/FVC < 70%; 30%  FEV1 < 50% predicted
With or without chronic symptoms (cough, sputum, dyspnea)
IV: Very Severe FEV1/FVC < 70%; FEV1 < 30% predicted or FEV1
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< 50% predicted plus chronic respiratory failure
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GOLD Workshop Report
Four Components of COPD
Management
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic
4. Manage exacerbations
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Reduce Risk Factors
Key Points
• Reduction of total personal exposure to tobacco
smoke, occupational dusts and chemicals, and
indoor and outdoor air pollutants are important goals
to prevent the onset and progression of COPD.
• Smoking cessation is the single most effective - and
cost effective - intervention to reduce the risk of
developing COPD and stop its progression
(Evidence A).
Reduce Risk Factors
Key Points
 Brief tobacco dependence treatment is effective
(Evidence A), and every tobacco user should be
offered at least this treatment at every visit to a
health care provider.
 Three types of counseling are especially effective:
practical counseling, social support as part of
treatment, and social support arranged outside of
treatment (Evidence A).
Reduce Risk Factors
Key Points
 Several effective pharmacotherapies for
tobacco dependence are available
(Evidence A), and at least one of these
medications should be added to
counseling if necessary, and in the
absence of contraindications.
Reduce Risk Factors
Key Points
 Progression of many occupationallyinduced respiratory disorders can be
reduced or controlled through a variety
of strategies aimed at reducing the
burden of inhaled particles and gases
(Evidence B).
Brief Strategies To Help The
Patient Willing To Quit Smoking
• ASK
• ADVISE
• ASSESS
• ASSIST
Systematically identify all
tobacco users at every visit.
Strongly urge all tobacco
users to quit.
Determine willingness to
make a quit attempt.
Aid the patient in quitting.
• ARRANGE Schedule follow-up contact.
GOLD Workshop Report
Four Components of COPD
Management
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic
4. Manage exacerbations
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Manage Stable COPD
Key Points

The overall approach to managing stable COPD
should be characterized by a stepwise increase in
the treatment, depending on the severity of the
disease.
For patients with COPD, health education can play a
role in improving skills, ability to cope with illness,
and health status. It is effective in accomplishing
certain goals, including smoking cessation
(Evidence A).
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
Manage Stable COPD
Key Points

None of the existing medications for COPD
has been shown to modify the long-term
decline in lung function that is the hallmark of
this disease (Evidence A). Therefore,
pharmacotherapy for COPD is used to
decrease symptoms and/or complications.
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Manage Stable COPD
Key Points

Bronchodilator medications are central to the
symptomatic management of COPD (Evidence A).
They are given on an as-needed basis or on a
regular basis to prevent or reduce symptoms.

The principal bronchodilator treatments are beta2agonists, anticholinergics, theophylline, and a
combination of these drugs (Evidence A).
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Bronchodilators in Stable
COPD

Bronchodilator medications are central to symptom
management in COPD.

Inhaled therapy is preferred.

The choice between beta2-agonist, anticholinergic,
theophylline, or combination therapy depends on
availability and individual response in terms of
symptom relief and side effects.
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Bronchodilators in Stable
COPD

Bronchodilators are prescribed on an as-needed or
on a regular basis to prevent or reduce symptoms.

Regular treatment with long-acting inhaled
bronchodilators is more effective and convenient
than treatment with short-acting bronchodilators, but
more expensive.

Combining bronchodilators may improve efficacy
and decrease the risk of side effects compared to
increasing the dose of a single bronchodilator.
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Manage Stable COPD
Key Points
Regular treatment with inhaled glucocorticosteroids
is appropriate for symptomatic COPD patients with
an FEV1 < 50% predicted (Stage III: Severe COPD
and Stage IV: Very Severe COPD) and repeated
exacerbations e.g. 3 in the last three years
(Evidence A).
 This treatment has been shown to reduce the
frequency of exacerbations and improve health
status (Evidence A). Dr. David P. Breen
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
Manage Stable COPD
Key Points

Chronic treatment with systemic glucocorticosteroids should be avoided because of an
unfavorable benefit-to-risk ratio (Evidence A).
 All COPD-patients benefit from exercise
training programs, improving with respect to
both exercise tolerance and symptoms of
dyspnea and fatigue (Evidence A).
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Manage Stable COPD
Key Points

The long-term administration of oxygen
(> 15 hours per day) to patients with
chronic respiratory failure has been
shown to increase survival (Evidence A).
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Management of COPD by
Severity of Disease
Stage 0: At risk
Stage I:
Mild COPD
Stage II: Moderate COPD
Stage III: Severe COPD
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Stage IV: Very Severe COPD
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Management of COPD:
All stages

Avoidance of risk factors
- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure

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Influenza vaccination
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Management of COPD
Stage 0: At Risk
Characteristics
Recommended Treatment
• Chronic symptoms
- cough
- sputum
• No spirometric
abnormalities
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Management of COPD
Stage I: Mild COPD
Characteristics
Recommended Treatment
• FEV1/FVC < 70 %
• FEV1 > 80 % predicted
• With or without chronic
symptoms
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• Short-acting
Dr. David P. Breen
bronchodilator as
needed
57
Management of COPD
Stage II: Moderate COPD
Characteristics
Recommended Treatment
• FEV1/FVC < 70%
• 50% < FEV1< 80% predicted
• With or without chronic
symptoms
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• Short-acting bronchodilator as needed
• Regular treatment with
one or more long-acting
bronchodilators
• Rehabilitation
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Management of COPD
Stage III: Severe COPD
Characteristics
Recommended Treatment
• FEV1/FVC < 70%
• 30% < FEV1 < 50% predicted
• With or without chronic
symptoms
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• Short-acting broncho-
dilator as needed
• Regular treatment
with one or more
long-acting
bronchodilators
• Inhaled glucocorticosteroids if repeated
exacerbations
Dr. David P. Breen
• Rehabilitation
59
Management of COPD
Stage IV: Very Severe COPD
Characteristics
Recommended Treatment
• Short-acting bronchodilator as
needed
• Regular treatment with one or
more long-acting bronchodilators
• Inhaled glucocorticosteroids if
repeated exacerbations
• Treat complications
• Rehabilitation
• Long-term oxygen therapy if
respiratory failure
Dr. David• P.Consider
Breen
60
surgical options
• FEV1/FVC < 70%
• FEV1 < 30% predicted or
FEV1 < 50% predicted
plus chronic respiratory
failure
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Therapy at Each Stage of COPD
Old (2001)
0: At Risk I: Mild
New
(2003)
0: At Risk I: Mild
Characteristics
Chronic
Symptoms
 Exposure to risk
factors
 Normal
spirometry

FEV1/FVC < 70%
 FEV1  80%
 With or without
symptoms

II: Moderate
IIA
IIB
II: Moderate III: Severe
III: Severe
FEV1/FVC < 70%
 50% < FEV1 < 80%
 With or without
symptoms


FEV1/FVC < 70%
 30% < FEV1 < 50%
 With or without
symptoms

IV: Very Severe
FEV1/FVC < 70%
 FEV1 < 30% or FEV1 < 50%
predicted plus chronic
respiratory failure
Avoidance of risk factor(s); influenza vaccination
Add short-acting bronchodilator when needed
Add regular treatment with one or more longacting bronchodilators
Add rehabilitation
Add inhaled glucocorticosteroids
if repeated exacerbations
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Dr. David P. Breen
Add long-term
oxygen if chronic
respiratory failure
61
Consider surgical
treatments
GOLD Workshop Report
Four Components of COPD
Management
1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic
4. Manage exacerbations
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62
Manage Exacerbations
Key Points

Exacerbations of respiratory symptoms
requiring medical intervention are important
clinical events in COPD.
The most common causes of an exacerbation
are infection of the tracheobronchial tree and
air pollution, but the cause of about one-third
of severe exacerbations cannot be identified
(Evidence
B).
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
Manage Exacerbations
Key Points

Inhaled bronchodilators (beta2-agonists
and/or anticholinergics), theophylline, and
systemic, preferably oral, glucocorticosteroids are effective for the treatment of
COPD exacerbations (Evidence A).
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Manage Exacerbations
Key Points

Patients experiencing COPD
exacerbations with clinical signs of
airway infection (e.g., increased volume
and change of color of sputum, and/or
fever) may benefit from antibiotic
treatment (Evidence B).
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Manage Exacerbations
Key Points

Noninvasive intermittent positive pressure
ventilation (NIPPV) in exacerbations improves
blood gases and pH, reduces in-hospital
mortality, decreases the need for invasive
mechanical ventilation and intubation, and
decreases the length of hospital stay
(Evidence A).
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Management of COPD

In selecting a treatment plan, the
benefits and risks to the individual,
and the direct and indirect costs to
the individual, his or her family, and
the community must be considered.
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Could it be COPD?
Do you know what COPD is? This chronic lung disease is a major cause of illness,
yet many people have it and don’t know it.
If you answer these questions, it will help you find out if you could have COPD.
1. Do you cough several times most days?
Yes ___ No ___
2. Do you bring up phlegm or mucus most days?
Yes ___ No ___
3. Do you get out of breath more easily than others your age? Yes ___ No ___
4. Are you older than 40 years?
Yes ___ No ___
5. Are you a current smoker or an ex-smoker?
Yes ___ No ___
If you answered yes to three or more of these questions, ask your doctor if you
might have COPD and should have a simple breathing test. If COPD is found early,
there are steps you can take to prevent further lung damage and make you feel
better.
18/Oct/2005
David lungs……Learn
P. Breen
Take time to think aboutDr.your
about COPD!
68
GOLD Website Address
http://www.goldcopd.com
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
Spirometry is the GOLD Standard for the
diagnosis of COPD
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Smoking Cessation
Pre-contemplator
Relapse
contemplation
Action
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
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Pharmacological treatment

1st line treatment
 Nicotine






replacement
Nicotine polacrilex (gum)
Transdermal nicotine
Nicotine inhaler
Nicotine nasal spray
Nicotine lozenges
Combined modality
 Bupropion

2nd line treatment
 Clonidine
 Nortripyline
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Management of Stable Disease





Smoking cessation
Pharmacological treatment
LTOT
Pulmonary rehabilitation
Surgery
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Pharmacological therapy




Medications can reduce or abolish symptoms,increase
exercise tolerance,reduce no and severity of symptoms and
improve health status
No treatment alters the rate of decline of lung function
Inhaled route is preferable – smaller doses and therefore
reduced side effects by inhalation
Combining agents have a greater effect on symptoms than
single agents
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General principles




Patients must be educated in the device
Choose right device for patient – MDI v DPI v
Spacer device
Spacer good for delivery and reduce oral s/e
Compliance is variable – studies show at east 85%
of patients take 70% of the prescribed doses - ?
Reflect the constant symptoms


Education is essential for good adherence and
proper use
Spirometry essential for diagnosis but not for
monitoring
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Bronchodilators



Β2 agonist
Anticholinergic agents
Methylxanthines
Mode of action is smooth muscle relaxation –
small changes in FEV but decreases in lung
volumes resulting in better emptying and less
hyperinflation
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Β2 agonist


Inhaled (short , long acting), oral
Mode of action



Increase in c-amp within cells and promote smooth
muscle relaxation
?other non bronchodilator effects
S/E
Palpitations, PVC
 Tremor
 Sleep disturbance
 Metabolic - hypokalaemia
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
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Anticholinergic drugs

Only available via inhaled route







Ipratropium
Oxitropium
Tiotropium
Inhibit muscarinic receptors
Tiotropium remains bound to receptors for up to 36 hours
Onset of bronchodilatation in 30 mins
S/E


Not associated with significant incidence of prostatism or cardiac S/E
Commonest – dry mouth(tiotropium), metallic taste (ipratropium),
closed angle glaucoma
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Methylxanthines






Oral or I.V prn preparations
Non specific PDE inhibitors and increase c-amp
Bronchodilatation only occurs at high dose and
narrow therapeutic/toxic window
Keep at level of 8-14 ug.dl
Can be bd or od drugs
S/E


Major – ventricular and atrial rhythm disturbance,
convulsions
Minor – headache, nausea, vomiting, diarrhoea and
heartburn
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Levels increased
Respiratory acidosis
CCF
Liver cirrhosis
Erthyromycin
ciprofloxacin
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Levels decreased
Cigarette smoke
Anti-convulsant drugs
rifampicin
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Glucocorticoids

Inhalation
 Beclomethasone
 Budesonide
 Triamcinolone
 Fluticasone
 Flunisolide

Oral
 Not
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indicated in stable – excessive S/E profile
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
Pharmacology



S/E




Effect transcription processes – slow action
High dose can be absorbed via the pulmonary circulation
Oral – osteoporosis, cataracts, peripheral myopathy
Topical/local S/E can be significant
Skin bruising
Clinical outcomes


If FEV<50% and a number of exacerbations/year rate of
deterioration in health status can be reduced
3 year prospective studies revealed no effect on rate of
decline of FEV1
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Combination therapy



Combination treatment is a convenient, safe
and improves compliance
Initial data show a significant effect on
pulmonary function and a reduction in
symptoms
Largest effects in most severe – FEV<50%
and a number of exacerbations
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Other agents




Mucolytic agents – carbocysteine, iodinated
glycerol
Little evidence of any effect on lung function
Cochrane review – supports a role for
reducing no of exacerbations in chronic
bronchitis
N-acetylcysteine – at present prospective
study ongoing
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

Leukotreine receptor antagonist -No data to support role
Maintenance antibiotic –no data to suggest that these drugs are
effective in modifying symptoms, exacerbations or lung function

Respiratory stimulants – oral peripheral chemoreceptor stimulant
– improves V/Q matching and improves oxygenation – can result in peripheral
neuropathy

Vaccination
Influenza – can reduce serious illness and death by
50%
 Pneumococcal – reduces bacteraemia

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Alpha1-antitrypsin deficiency





Augmentation therapy
Licensed for i.v. use twice a week
Expensive
No RCT showing benefit
Suggestio that rate of decline in those
receiving drug is less than historical controls.
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